The primary objective of this research proposal is to determine the mechanisms of action of somatomedin (SM) on target cells and tissues, and to relate such to the regulation of normal and abnormal growth and metabolism. Both receptor and post-receptor mechanisms will be studied to determine whether any defect(s) exist in the pathways mediating SM activity in certain clinical disorders, including idiopathic short stature, diabetes mellitus and obesity. Because its molecular structure is known, the SM insulin-like growth factor (IGF) will be employed as the SM prototype in these studies. The putative role of SM carrier protein in regulating the biologic activity of IGF will be studied, and efforts made to extract and purify a SM-mediator substance from target cells known to be responsive to IGF. Studies will aso be directed toward dissecting the separate effector pathways leading to the growth-promoting as well as the insulin-like activities of SM in various target cells.